Valence tautomerism in synthetic models of cytochrome P450

Abstract

CytP450s have a cysteine-bound heme cofactor that, in its asisolated resting (oxidized) form, can be conclusively described as a ferric thiolate species. Unlike the native enzyme, most synthetic thiolate-bound ferric porphyrins are unstable in air unless the axial thiolate ligand is sterically protected. Spectroscopic investigations on a series of synthetic mimics of cytP450 indicate that a thiolatebound ferric porphyrin coexists in organic solutions at room temperature (RT) with a thiyl-radical bound ferrous porphyrin, i.e., its valence tautomer. The ferric thiolate state is favored by greater enthalpy and is air stable. The ferrous thiyl state is favored by entropy, populates at RT, and degrades in air. These ground states can be reversibly interchanged at RT by the addition or removal of water to the apolar medium. It is concluded that hydrogen bonding and local electrostatics protect the resting oxidized cytP450 active site from degradation in air by stabilizing the ferric thiolate ground state in contrast to its synthetic analogs.valence tautomerism | cytochrome P450 | synthetic model | entropic contribution | hydrogen bonding

Competition of van der Waals and chemical forces on gold–sulfur surfaces and nanoparticles

“…The valence tautomerization example considers the bond between the iron of the heme group in cytochrome P450 and an attached cystyl ligand. 21…”

“…The evidence supporting this analysis is summarized in Box 1. 21 Related aspects of tautomerism apply also to the iron/heme/oxygen ligand interactions in the heme peroxidases and catalases. 22 Valence tautomerisation is like any isomerization reaction and is equivalent, for example, to the pyramidal inversion that interchanges the orientation of the molecular dipole in ammonia.…”

Advances in Computational Prediction of Regioselective and Isoform-Specific Drug Metabolism Catalyzed by CYP450s.

“…Sason Shaik and his co‐authors (in addition to the work on organometallic reactivity) have over many years pioneered the QM and QM/MM methodologies for solving regioselectivity problems in the oxidation of camphor and other small molecule system . These studies have established facts like two‐state reactivity concepts, chameleon character of CYP450, influence of the axial ligand, and use of valence bond concept in understanding the CYP450 reactivity . These studies by the Sason Shaik's group and other groups spanning over 30 years have laid the foundations on which new generation of computational chemists are building on to further understand the mysteries of regioselective, isoform specific and stereoselective CYP450 mediated chemistry and biology.…”

Spin Changes Accompany Ultrafast Structural Interconversion in the Ground State of a Cobalt Nitrosyl Complex

“…[4] Theo xidation states of the Co are nominally + Ii nt he TBP and + III in the SP complexes.Structural isomerization is therefore accompanied by achange in the formal oxidation state of the Co atom, and the isomers are valence tautomers. [5] Figure 2s hows molecular orbital (MO) diagrams for 5coordinate cobalt nitrosyl complexes with four identical ligands. [4] TheT BP and SP geometries are associated with singlet and triplet states,respectively.Inthe SP complex, the {d yz ; p * y NO ðÞ }o rbital is stabilized through interactions with the other ligands,b ringing it close enough in energy to the {d xz ; sp 2 N ðÞ }MOthat atriplet spin-state becomes the ground electronic configuration.…”